Meyer Andreas, Schürmann Peter, Ghahremani Maryam, Kocak Ertan, Brinkhaus Maria-Jantje, Bremer Michael, Karstens Johann H, Hagemann Jörn, Machtens Stefan, Dörk Thilo
Hannover Prostate Cancer Study Group, Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
Urol Oncol. 2009 Jul-Aug;27(4):373-6. doi: 10.1016/j.urolonc.2008.04.010. Epub 2008 Jul 14.
Genetic susceptibility contributes to the risk of prostate cancer but the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies.
We aimed to define the risks associated with two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital-based series of prostate cancer patients treated with brachytherapy.
We analyzed genomic DNA samples of 488 prostate cancer cases undergoing brachytherapy at Hannover Medical School, and of 462 male controls from the same location. Genotyping was performed using 5'-exonuclease allelic discrimination assays, and results were evaluated with chi(2) tests and logistic regression analyses.
We investigated whether rs1447295 and rs13281615 are associated with disease risk in a hospital-based prostate cancer case-control series from Northern Germany. The rare allele of rs1447295 was observed at higher frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P = 0.01), and there was a dose-dependent trend towards a higher prevalence of heterozygous and homozygous carriers among the prostate cancer patients (per allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI 0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was significantly different between cases and controls (P = 0.01).
Our results corroborate previous reports of 8q24 as a prostate cancer susceptibility locus and provide evidence for rs1447295 as a potentially important genetic marker. Further studies are required to confirm whether the adjacent breast cancer-associated variant rs13281615 may be inversely associated with prostate cancer risk.
遗传易感性会增加患前列腺癌的风险，但潜在基因在很大程度上尚不清楚。全基因组关联研究表明，8号染色体q24区域的多态性位点可能是乳腺癌和前列腺癌的风险因素。
我们旨在确定在接受近距离放射治疗的前列腺癌患者的医院系列研究中，两个单核苷酸多态性（rs1447295和rs13281615）相关的风险。
我们分析了汉诺威医学院488例接受近距离放射治疗的前列腺癌病例以及来自同一地区的462名男性对照的基因组DNA样本。使用5'-外切酶等位基因鉴别分析进行基因分型，并通过卡方检验和逻辑回归分析评估结果。
我们在德国北部一个基于医院的前列腺癌病例对照系列研究中，调查了rs1447295和rs13281615是否与疾病风险相关。rs1447295的罕见等位基因在病例中的出现频率高于基于医院的对照（13.9%对10.2%，P = 0.01），并且在前列腺癌患者中杂合子和纯合子携带者的患病率存在剂量依赖性升高趋势（每个等位基因的比值比为1.42，95%置信区间为1.07；1.87，P = 0.02）。相比之下，rs13281615的罕见等位基因不会增加患前列腺癌的风险（每个等位基因的比值比为0.84，95%置信区间为0.70；1.00，P = 0.05）。病例组和对照组中8q24联合基因型的分布存在显著差异（P = 0.01）。
我们的结果证实了先前关于8q24是前列腺癌易感位点的报道，并为rs1447295作为潜在重要遗传标记提供了证据。需要进一步研究以确认相邻的与乳腺癌相关的变异rs13281615是否可能与前列腺癌风险呈负相关。
